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HIV-1 Transmission by Dendritic Cell-specific ICAM-3-grabbing Nonintegrin (DC-SIGN) Is Regulated by Determinants in the Carbohydrate Recognition Domain That Are Absent in Liver/Lymph Node-SIGN (L-SIGN)

  1. Author:
    Chung, N. P. Y.
    Breun, S. K. J.
    Bashirova, A.
    Baumann, J. G.
    Martin, T. D.
    Karamchandani, J. M.
    Rausch, J. W.
    Le Grice, S. F. J.
    Wu, L.
    Carrington, M.
    KewalRamani, V. N.

  2. Author Address

    [Chung, Nancy P. Y.; Martin, Thomas D.; Karamchandani, Jaideep M.; Rausch, Jason W.; Le Grice, Stuart F. J.; KewalRamani, Vineet N.] NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21702 USA. [Breun, Sabine K. J.; Baumann, Joerg G.] Fraunhofer Inst Cell Therapy & Immunol, D-04103 Leipzig, Germany. [Bashirova, Arman; Carrington, Mary] NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick,NIH, Frederick, MD 21702 USA. [Wu, Li] Med Coll Wisconsin, Dept Microbiol & Mol Genet, Milwaukee, WI 53226 USA.;KewalRamani, VN, NCI, HIV Drug Resistance Program, NIH, 1050 Boyles St, Frederick, MD 21702 USA.;vineet@mail.nih.gov
    1. Year: 2010
    2. Date: Jan 15
    3. Epub Date: 10/17/2009
  2. Journal: Journal of Biological Chemistry
    1. 285
    2. 3
    3. Pages: 2100-2112
  4. Type of Article: Article
  5. ISSN: 0021-9258
  1. Abstract:

    In this study, we identify determinants in dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) necessary for human immunodeficiency virus, type 1 (HIV-1), transmission. Although human B cell lines expressing DC-SIGN efficiently capture and transmit HIV-1 to susceptible target cells, cells expressing the related molecule liver/lymph node-specific ICAM-3-grabbing nonintegrin (L-SIGN) do not. To understand the differences between DC-SIGN and L-SIGN that affect HIV-1 interactions, we developed Raji B cell lines expressing different DC-SIGN/L-SIGN chimeras. Testing of the chimeras demonstrated that replacement of the DC-SIGN carbohydrate-recognition domain (CRD) with that of L-SIGN was sufficient to impair virus binding and prevent transmission. Conversely, the ability to bind and transmit HIV-1 was conferred to L-SIGN chimeras containing the DC-SIGN CRD. We identified Trp-258 in the DC-SIGN CRD to be essential for HIV-1 transmission. Although introduction of a K270W mutation at the same position in L-SIGN was insufficient for HIV-1 binding, an L-SIGN mutant molecule with K270W and a C-terminal DC-SIGN CRD subdomain transmitted HIV-1. These data suggest that DC-SIGN structural elements distinct from the oligosaccharide-binding site are required for HIV-1 glycoprotein selectivity.

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External Sources

  1. View Full Text
  2. DOI: 10.1074/jbc.M109.030619
  3. PMID: 19833723
  4. PMCID: PMC2804366
  5. View record in Web of Science®
  6. WOS: 000273429100054

Library Notes

  1. Fiscal Year: FY2009-2010
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